We plan to investigate the sites of intracellular CO stores in anesthetized dogs. Effects of elevated body CO stores on metabolic ex-cretion of CO and on peripheral oxygenation of tissues will be investigated. Using a method where mean myoglobin PO2 can be estimated frm measurements of binding of CO to myoglobin we will investigate the relationships of changes in skeletal muscle circulation to changes in intracellular PO2. We will investigate the mechanisms of oxygen autoregulation of skeletal muscle includ-ing the mechanism of effects of oxygen on vascular smooth muscle and the poss-ibility that the prostaglandin synthetase system can be an oxygen tension sensor. We will study the pathophysiology of oxygeneration of skeletal muscle in patients with pulmonary and cardiac disease, using CO binding to myoglobin as an indicator of intracellular PO2.